DOI: 10.1101/498899Dec 18, 2018Paper

A metabolic switch from OXPHOS to glycolysis is essential for cardiomyocyte proliferation in the regenerating heart

BioRxiv : the Preprint Server for Biology
Hessel HonkoopJeroen Bakkers

Abstract

The capacity to regenerate damaged tissues, such as the heart, various enormously amongst species. While heart regeneration is generally very low in mammals, it can regenerate efficiently in certain amphibian and fish species. Zebrafish has been used extensively to study heart regeneration, resulting in the identification of proliferating cardiomyocytes that drive this process. However, mechanisms that drive cardiomyocyte proliferation are largely unknown. Here, using a single-cell mRNA-sequencing approach, we find a transcriptionally distinct population of dedifferentiated and proliferating cardiomyocytes in regenerating zebrafish hearts. While adult cardiomyocytes are known to rely on mitochondrial oxidative phosphorylation (OXPHOS) for energy production, these proliferating cardiomyocytes show reduced mitochondrial gene expression and decreased OXPHOS activity. Strikingly, we find that genes encoding rate-limiting enzymes of the glycolysis pathway are induced in the proliferating cardiomyocytes, and inhibiting glycolysis impairs cardiomyocyte cell cycle reentry. Mechanistically, glycolytic gene expression is induced by Nrg1/Erbb2 signaling, and this is conserved in a mouse model of enhanced regeneration. Moreover, inhibiting...Continue Reading

Related Concepts

Amphibians
Cell Cycle
Energy Transfer
Gene Expression
Genes
Glycolysis
Heart
Mus
Oxidative Phosphorylation
Natural Regeneration

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